RNA interference (RNAi) is the mechanism of sequence-specific, post-transcriptional gene silencing initiated by double-stranded RNAs (dsRNA) homologous to the gene being suppressed. dsRNAs are processed by Dicer, a cellular ribonuclease III, to generate duplexes of about 21 nt with 3′-overhangs (small interfering RNA, siRNA) which mediate sequence-specific mRNA degradation. In mammalian cells siRNA molecules are capable of specifically silencing gene expression without induction of the unspecific interferon response pathway. Thus, siRNAs have become a new and powerful alternative to other genetic tools such as antisense oligonucleotides and ribozymes to analyze gene function. Moreover, siRNAs are being developed for therapeutic purposes with the aim of silencing disease genes in humans.
A key problem in the development of effective gene therapy techniques is the delivery of nucleic acids to cells in vivo. The formation of stable complexes between negatively charged genetic material and cationic polymers is the most commonly studied approach to develop non-viral delivery agents. The work of several groups has focused on synthesizing and characterizing a range of cationic polymers to provide good DNA condensation necessary to prevent degradation of the genetic material in negatively charged nanoparticles capable of DNA delivery into cells. Once inside the cells, these nanocomplexes should be capable of releasing DNA, and the toxicity of the free cationic polymer must be minimal. Polyethylenimine (PEI) has proven to be one of the best cationic polymers for nanocomplex formation with DNA and provides good transfection efficiencies; however PEI is toxic to cells, thus limiting the concentration range that can be used. The goal of producing delivery agents that are non-toxic, capable of efficiently protecting DNA and delivering DNA to the interiors of cells has proven challenging, and an ideal gene delivery system remains elusive.